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Platelet-Activating Factor Stimulates Interleukin-6 Production by Human Endothelial Cells and Synergizes with Tumor Necrosis Factor for Enhanced Production of Granulocyte-Macrophage Colony Stimulating Factor

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Abstract

The interaction between human endothelial cells (EC) and leukocytes during inflammation is in part mediated through the release of soluble factors. Since platelet-activating factor (PAF) is a potent mediator of inflammatory responses, we investigated the potential of PAF to modulate IL-6 and GM-CSF production by EC. Exposure of these cells to PAF resulted in a concentration-dependent increase in IL-6 production, with a maximum at 10−10 M PAF. Sequential incubation of EC with PAF and TNFα resulted in a synergistic increase of IL-6 production. This effect was specific for PAF since it was prevented by preincubation with the PAF receptor antagonist, WEB 2086. Northern blot analysis revealed enhanced IL-6 mRNA expression in PAF-treated EC. However, the synergy observed in protein synthesis between PAF and TNFα was not reflected in IL-6 mRNA accumulation, suggesting a post-translational modulation. Pretreatment of EC with the protein synthesis inhibitor cycloheximide before their exposure to PAF resulted, after washout of the cycloheximide, in a markedly augmented production of IL-6, suggesting a synergy between augmented IL-6 mRNA accumulation by PAF and IL-6 mRNA superinduction by cycloheximide. GM-CSF production by EC was also stimulated by the combined effects of PAF and TNFα, but PAF alone did not affect GM-CSF production. Taken together, our data suggest that PAF can stimulate EC to synthesize cytokines, including IL-6 and GM-CSF, which may contribute to local and, possibly, systemic responses during inflammation.

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  1. Chantal Lacasse

    Present address: Phoenix International Life Sciences Inc., Montréal, QC, Canada

Authors and Affiliations

  1. Immunology Division, Department of Pediatrics, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada, J1H 4N4

    Sylvie Turcotte, Denis Gingras, Jana Stankova & Marek Rola-Pleszczynski

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Lacasse, C., Turcotte, S., Gingras, D. et al. Platelet-Activating Factor Stimulates Interleukin-6 Production by Human Endothelial Cells and Synergizes with Tumor Necrosis Factor for Enhanced Production of Granulocyte-Macrophage Colony Stimulating Factor. Inflammation 21, 145–158 (1997). https://doi.org/10.1023/A:1027314103063

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